Although a considerable body of research has focused on the neural substrates of social separation, relatively little is known about the neurobiology of social attachment. This proposal focuses on a monogamous rodent, the prairie vole (Microtus ochrogaster), which is distinguished by the formation of selective, enduring social attachments or pair bonds. Several lines of evidence implicate central oxytocin (OT) pathways in prairie vole pair bond formation. OT increases and a selective OT antagonist decreases mating-induced pair bonding in female prairie voles as measured by the development of a partner preference. We propose four new studies to investigate the mechanisms by which OT facilitates social attachment. The first study extends earlier work on the importance of mating for prairie vole pair bonding by investigating the effects of mating on OT pathways in the prairie vole brain. This experiment will compare monogamous prairie voles with non-monogamous montane voles (M. montanus), which show similar patterns of mating behavior but fail to form enduring, selective social attachments. The second study will extend earlier results of the blockade of pair bonding with an OT antagonist by using site-specific injections of an OT antagonist to localize the pathways critical for social attachment in the monogamous prairie vole. A third study will investigate cognitive mechanisms by which OT facilitates partner preference formation, including studies of memory, neophobia, and reinforcement. Finally, a fourth study explores molecular mechanisms for differences in OT receptor expression in monogamous and non-monogamous voles, using a transgenic approach. Taken together, these studies should provide a comprehensive understanding of the role of central OT pathways in the process of social attachment. By adopting a comparative approach, these studies may reveal not only a proximate mechanism by which mating and OT facilitate pair bonding, but also suggest how a specific neuroendocrine system has been adapted for quite different behavioral functions in closely related species. The ultimate goal of this work is to provide a basic understanding of the neurobiology of attachment with the hope that this knowledge will inform approaches to clinical disorders characterized by deficits in attachment, including autism and schizophrenia.